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Erschienen in: Journal of Children's Orthopaedics 1/2012

01.03.2012 | Original Clinical Article

Complications of pamidronate therapy in paediatric osteoporosis

verfasst von: Sanjay K. Chilbule, Vrisha Madhuri

Erschienen in: Journal of Children's Orthopaedics | Ausgabe 1/2012

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Abstract

Purpose

Pamidronate, used for the treatment of paediatric osteoporosis, reduces the fracture rate and improves ambulatory status. Intravenous pamidronate therapy has known complications which have not been stratified based on its dose and distribution. This study aims to assess the early minor and major medical and late surgical complications and the effect of the dose and regimen of infusion on these events in paediatric osteoporosis.

Study design

Retrospective cohort.

Materials and methods

Three regimens for pamidronate infusion were followed in sequential periods in 10 years. Regimen A delivered 1.5 mg/kg/day as a single dose once in 3 months. Regimen B delivered 2 mg/kg/day for 3 days twice a year, while regimen C delivered 1 mg/kg/day for 3 days every 3–4 months. Adverse events were classified as early (major and minor) or late (surgical).

Results

Forty-eight children received 158 infusions using one of the three regimens. Twenty-nine complications occurred in 24 children. A significant difference in the complication rate was present among the three regimens (P = 0.005). Nineteen children had minor complications, mainly febrile reaction or asymptomatic hypocalcaemia. Four major complications consisting of one seizure, one respiratory distress and two hypocalcaemic tetany were encountered, all with regimen B. Intraoperative complication faced was loss of position due to splintering of the cortex while rush rodding. This was seen in 20% of the long bone segments operated in those who received pamidronate as compared to 4.4% of the segments which were operated prior to the initiation of pamidronate therapy; the odds of splintering were 5.4 times higher for those patients who were bone segment rodded after pamidronate therapy.

Discussion

Intravenous pamidronate is associated with complications in 50% of children with paediatric osteoporosis, with a dose-dependent significant difference. Major complications are not uncommon with higher doses and can be avoided by increasing the number of doses per year and decreasing the dose per cycle. Surgical difficulty, when possible, can be avoided by correcting any major deformities at presentation prior to the induction of pamidronate therapy.
Literatur
1.
Zurück zum Zitat Hoekman K, Papapoulos SE, Peters AC, Bijvoet OL (1985) Characteristics and bisphosphonate treatment of a patient with juvenile osteoporosis. J Clin Endocrinol Metab 61(5):952–956PubMedCrossRef Hoekman K, Papapoulos SE, Peters AC, Bijvoet OL (1985) Characteristics and bisphosphonate treatment of a patient with juvenile osteoporosis. J Clin Endocrinol Metab 61(5):952–956PubMedCrossRef
2.
Zurück zum Zitat Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 339(14):947–952PubMedCrossRef Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 339(14):947–952PubMedCrossRef
3.
Zurück zum Zitat Shaw NJ (2008) Management of osteoporosis in children. Eur J Endocrinol 159(Suppl 1):S33–S39PubMedCrossRef Shaw NJ (2008) Management of osteoporosis in children. Eur J Endocrinol 159(Suppl 1):S33–S39PubMedCrossRef
4.
6.
Zurück zum Zitat Wijewardena SK, Kekulawala C, de Silva PDN, de Almeida M, Perera BJC (2010) Bisphosphonate treatment for type III osteogenesis imperfecta in Lady Ridgeway Hospital, Colombo, Sri Lanka. Sri Lanka J Child Health 39:44–46CrossRef Wijewardena SK, Kekulawala C, de Silva PDN, de Almeida M, Perera BJC (2010) Bisphosphonate treatment for type III osteogenesis imperfecta in Lady Ridgeway Hospital, Colombo, Sri Lanka. Sri Lanka J Child Health 39:44–46CrossRef
7.
Zurück zum Zitat Rauch F, Travers R, Plotkin H, Glorieux FH (2002) The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest 110(9):1293–1299PubMedPubMedCentralCrossRef Rauch F, Travers R, Plotkin H, Glorieux FH (2002) The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest 110(9):1293–1299PubMedPubMedCentralCrossRef
8.
Zurück zum Zitat Bachrach LK, Ward LM (2009) Clinical review 1: bisphosphonate use in childhood osteoporosis. J Clin Endocrinol Metab 94(2):400–409PubMedCrossRef Bachrach LK, Ward LM (2009) Clinical review 1: bisphosphonate use in childhood osteoporosis. J Clin Endocrinol Metab 94(2):400–409PubMedCrossRef
9.
Zurück zum Zitat Chien YH, Chu SY, Hsu CC, Hwu WL (2002) Pamidronate treatment of severe osteogenesis imperfecta in a newborn infant. J Inherit Metab Dis 25(7):593–595PubMedCrossRef Chien YH, Chu SY, Hsu CC, Hwu WL (2002) Pamidronate treatment of severe osteogenesis imperfecta in a newborn infant. J Inherit Metab Dis 25(7):593–595PubMedCrossRef
10.
Zurück zum Zitat Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH (2004) Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res 19(11):1779–1786PubMedCrossRef Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH (2004) Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res 19(11):1779–1786PubMedCrossRef
11.
Zurück zum Zitat Munns CF, Rauch F, Mier RJ, Glorieux FH (2004) Respiratory distress with pamidronate treatment in infants with severe osteogenesis imperfecta. Bone 35(1):231–234PubMedCrossRef Munns CF, Rauch F, Mier RJ, Glorieux FH (2004) Respiratory distress with pamidronate treatment in infants with severe osteogenesis imperfecta. Bone 35(1):231–234PubMedCrossRef
12.
Zurück zum Zitat Bajpai A, Kabra M, Gupta N, Sharda S, Ghosh M (2007) Intravenous pamidronate therapy in osteogenesis imperfecta: response to treatment and factors influencing outcome. J Pediatr Orthop 27(2):225–227PubMedCrossRef Bajpai A, Kabra M, Gupta N, Sharda S, Ghosh M (2007) Intravenous pamidronate therapy in osteogenesis imperfecta: response to treatment and factors influencing outcome. J Pediatr Orthop 27(2):225–227PubMedCrossRef
13.
Zurück zum Zitat Castillo H, Samson-Fang L; American Academy for Cerebral Palsy and Developmental Medicine Treatment Outcomes Committee Review Panel (2009) Effects of bisphosphonates in children with osteogenesis imperfecta: an AACPDM systematic review. Dev Med Child Neurol 51(1):17–29PubMedCrossRef Castillo H, Samson-Fang L; American Academy for Cerebral Palsy and Developmental Medicine Treatment Outcomes Committee Review Panel (2009) Effects of bisphosphonates in children with osteogenesis imperfecta: an AACPDM systematic review. Dev Med Child Neurol 51(1):17–29PubMedCrossRef
14.
Zurück zum Zitat Steelman J, Zeitler P (2003) Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. J Pediatr 142(4):417–423PubMedCrossRef Steelman J, Zeitler P (2003) Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. J Pediatr 142(4):417–423PubMedCrossRef
15.
Zurück zum Zitat Phillipi CA, Remmington T, Steiner RD (2008) Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 8(4):CD005088 Phillipi CA, Remmington T, Steiner RD (2008) Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 8(4):CD005088
16.
Zurück zum Zitat Alharbi M, Pinto G, Finidori G, Souberbielle JC, Guillou F, Gaubicher S, Le Merrer M, Polak M (2009) Pamidronate treatment of children with moderate-to-severe osteogenesis imperfecta: a note of caution. Horm Res 71(1):38–44PubMedCrossRef Alharbi M, Pinto G, Finidori G, Souberbielle JC, Guillou F, Gaubicher S, Le Merrer M, Polak M (2009) Pamidronate treatment of children with moderate-to-severe osteogenesis imperfecta: a note of caution. Horm Res 71(1):38–44PubMedCrossRef
17.
Zurück zum Zitat Papapoulos SE, Cremers SC (2007) Prolonged bisphosphonate release after treatment in children. N Engl J Med 356(10):1075–1076PubMedCrossRef Papapoulos SE, Cremers SC (2007) Prolonged bisphosphonate release after treatment in children. N Engl J Med 356(10):1075–1076PubMedCrossRef
19.
Zurück zum Zitat Whyte MP, McAlister WH, Novack DV, Clements KL, Schoenecker PL, Wenkert D (2008) Bisphosphonate-induced osteopetrosis: novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res 23(10):1698–1707PubMedCrossRef Whyte MP, McAlister WH, Novack DV, Clements KL, Schoenecker PL, Wenkert D (2008) Bisphosphonate-induced osteopetrosis: novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res 23(10):1698–1707PubMedCrossRef
20.
Zurück zum Zitat Tanvetyanon T, Stiff PJ (2006) Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol 17(6):897–907PubMedCrossRef Tanvetyanon T, Stiff PJ (2006) Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol 17(6):897–907PubMedCrossRef
21.
Zurück zum Zitat Fraunfelder FW, Fraunfelder FT, Jensvold B (2003) Scleritis and other ocular side effects associated with pamidronate disodium. Am J Ophthalmol 135(2):219–222PubMedCrossRef Fraunfelder FW, Fraunfelder FT, Jensvold B (2003) Scleritis and other ocular side effects associated with pamidronate disodium. Am J Ophthalmol 135(2):219–222PubMedCrossRef
22.
Zurück zum Zitat Martinez-Soto T, Pacaud D, Stephure D, Trussell R, Huang C (2011) Treatment of symptomatic osteoporosis in children: a comparison of two pamidronate dosage regimens. J Pediatr Endocrinol Metab 24(5–6):271–274PubMed Martinez-Soto T, Pacaud D, Stephure D, Trussell R, Huang C (2011) Treatment of symptomatic osteoporosis in children: a comparison of two pamidronate dosage regimens. J Pediatr Endocrinol Metab 24(5–6):271–274PubMed
23.
Zurück zum Zitat Senthilnathan S, Walker E, Bishop NJ (2008) Two doses of pamidronate in infants with osteogenesis imperfecta. Arch Dis Child 93(5):398–400PubMedCrossRef Senthilnathan S, Walker E, Bishop NJ (2008) Two doses of pamidronate in infants with osteogenesis imperfecta. Arch Dis Child 93(5):398–400PubMedCrossRef
24.
Zurück zum Zitat El-Sobky MA, Hanna AA, Basha NE, Tarraf YN, Said MH (2006) Surgery versus surgery plus pamidronate in the management of osteogenesis imperfecta patients: a comparative study. J Pediatr Orthop B 15(3):222–228PubMedCrossRef El-Sobky MA, Hanna AA, Basha NE, Tarraf YN, Said MH (2006) Surgery versus surgery plus pamidronate in the management of osteogenesis imperfecta patients: a comparative study. J Pediatr Orthop B 15(3):222–228PubMedCrossRef
25.
Zurück zum Zitat DiMeglio LA, Peacock M (2006) Two-year clinical trial of oral alendronate versus intravenous pamidronate in children with osteogenesis imperfecta. J Bone Miner Res 21(1):132–140PubMedCrossRef DiMeglio LA, Peacock M (2006) Two-year clinical trial of oral alendronate versus intravenous pamidronate in children with osteogenesis imperfecta. J Bone Miner Res 21(1):132–140PubMedCrossRef
26.
Zurück zum Zitat Grissom LE, Kecskemethy HH, Bachrach SJ, McKay C, Harcke HT (2005) Bone densitometry in pediatric patients treated with pamidronate. Pediatr Radiol 35(5):511–517PubMedCrossRef Grissom LE, Kecskemethy HH, Bachrach SJ, McKay C, Harcke HT (2005) Bone densitometry in pediatric patients treated with pamidronate. Pediatr Radiol 35(5):511–517PubMedCrossRef
27.
Zurück zum Zitat Poyrazoglu S, Gunoz H, Darendeliler F, Bas F, Tutunculer F, Eryilmaz SK, Bundak R, Saka N (2008) Successful results of pamidronate treatment in children with osteogenesis imperfecta with emphasis on the interpretation of bone mineral density for local standards. J Pediatr Orthop 28(4):483–487PubMedCrossRef Poyrazoglu S, Gunoz H, Darendeliler F, Bas F, Tutunculer F, Eryilmaz SK, Bundak R, Saka N (2008) Successful results of pamidronate treatment in children with osteogenesis imperfecta with emphasis on the interpretation of bone mineral density for local standards. J Pediatr Orthop 28(4):483–487PubMedCrossRef
28.
29.
Zurück zum Zitat Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, Travers R, Glorieux FH (2000) Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 85(5):1846–1850PubMed Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, Travers R, Glorieux FH (2000) Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 85(5):1846–1850PubMed
30.
Zurück zum Zitat Russell RG (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119(Suppl 2):S150–S162PubMedCrossRef Russell RG (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119(Suppl 2):S150–S162PubMedCrossRef
31.
32.
Zurück zum Zitat Jakubowska-Pietkiewicz E, Chlebna-Sokół D (2008) New trends in the treatment of osteogenesis imperfecta type III—own experience. Ortop Traumatol Rehabil 10(6):593–601PubMed Jakubowska-Pietkiewicz E, Chlebna-Sokół D (2008) New trends in the treatment of osteogenesis imperfecta type III—own experience. Ortop Traumatol Rehabil 10(6):593–601PubMed
33.
Zurück zum Zitat Diel IJ, Bergner R, Grötz KA (2007) Adverse effects of bisphosphonates: current issues. J Support Oncol 5(10):475–482PubMed Diel IJ, Bergner R, Grötz KA (2007) Adverse effects of bisphosphonates: current issues. J Support Oncol 5(10):475–482PubMed
34.
Zurück zum Zitat Meyers PA, Healey JH, Chou AJ, Wexler LH, Merola PR, Morris CD, Laquaglia MP, Kellick MG, Abramson SJ, Gorlick R (2011) Addition of pamidronate to chemotherapy for the treatment of osteosarcoma. Cancer 117(8):1736–1744PubMedPubMedCentralCrossRef Meyers PA, Healey JH, Chou AJ, Wexler LH, Merola PR, Morris CD, Laquaglia MP, Kellick MG, Abramson SJ, Gorlick R (2011) Addition of pamidronate to chemotherapy for the treatment of osteosarcoma. Cancer 117(8):1736–1744PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Forin V, Arabi A, Guigonis V, Filipe G, Bensman A, Roux C (2005) Benefits of pamidronate in children with osteogenesis imperfecta: an open prospective study. Joint Bone Spine 72(4):313–318PubMedCrossRef Forin V, Arabi A, Guigonis V, Filipe G, Bensman A, Roux C (2005) Benefits of pamidronate in children with osteogenesis imperfecta: an open prospective study. Joint Bone Spine 72(4):313–318PubMedCrossRef
36.
Zurück zum Zitat Agarwal V, Joseph B (2005) Non-union in osteogenesis imperfecta. J Pediatr Orthop B 14(6):451–455PubMedCrossRef Agarwal V, Joseph B (2005) Non-union in osteogenesis imperfecta. J Pediatr Orthop B 14(6):451–455PubMedCrossRef
37.
Zurück zum Zitat Wray JB (1965) Factors in the pathogenesis of non-union. J Bone Joint Surg Am 47(1):168–173PubMed Wray JB (1965) Factors in the pathogenesis of non-union. J Bone Joint Surg Am 47(1):168–173PubMed
38.
Zurück zum Zitat Firoozbakhsh K, Moneim MS, Mikola E, Haltom S (2003) Heat generation during ulnar osteotomy with microsagittal saw blades. Iowa Orthop J 23:46–50PubMedPubMedCentral Firoozbakhsh K, Moneim MS, Mikola E, Haltom S (2003) Heat generation during ulnar osteotomy with microsagittal saw blades. Iowa Orthop J 23:46–50PubMedPubMedCentral
39.
Zurück zum Zitat Miettunen PM, Wei X, Kaura D, Reslan WA, Aguirre AN, Kellner JD (2009) Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol Online J 7:2PubMedPubMedCentralCrossRef Miettunen PM, Wei X, Kaura D, Reslan WA, Aguirre AN, Kellner JD (2009) Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol Online J 7:2PubMedPubMedCentralCrossRef
Metadaten
Titel
Complications of pamidronate therapy in paediatric osteoporosis
verfasst von
Sanjay K. Chilbule
Vrisha Madhuri
Publikationsdatum
01.03.2012
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Children's Orthopaedics / Ausgabe 1/2012
Print ISSN: 1863-2521
Elektronische ISSN: 1863-2548
DOI
https://doi.org/10.1007/s11832-012-0383-5

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